Opposite regulation of inhibition by adult-born granule cells during implicit versus explicit olfactory learning

Abstract

Both passive exposure and active learning through reinforcement enhance fine sensory discrimination abilities. In the olfactory system, this enhancement is thought to occur partially through the integration of adult-born inhibitory interneurons resulting in a refinement of the representation of overlapping odorants. Here, we identify in mice a novel and unexpected dissociation between passive and active learning at the level of adult-born granule cells. Specifically, while both passive and active learning processes augment neurogenesis, adult-born cells differ in their morphology, functional coupling and thus their impact on olfactory bulb output. Morphological analysis, optogenetic stimulation of adult-born neurons and mitral cell recordings revealed that passive learning induces increased inhibitory action by adult-born neurons, probably resulting in more sparse and thus less overlapping odor representations. Conversely, after active learning inhibitory action is found to be diminished due to reduced connectivity. In this case, strengthened odor response might underlie enhanced discriminability.

Young adult-born neurons improve odor coding by mitral cells

“…Remarkably, this inferred property was indeed observed empirically. This prediction is consistent with well-established findings from anatomy and slice electrophysiology, which showed that the abGCs-to-MCs synapses are purely inhibitory 12,15,23 . In addition, in vivo recordings of MCs spontaneous activity showed a decrease in MCs activity when abNs were activated (Alonso et al 15 ).…”

Context-dependent plasticity of adult-born neurons regulated by cortical feedback

“…Previous studies with slice electrophysiology and postmortem histology showed that young abGCs are highly plastic (11,32) and that learning induces spine density increase in abGCs (30,34). Here, our in vivo longitudinal imaging showed that the spine increase in abGCs occurs gradually and cumulatively over days of perceptual learning by increasing new spine formation and decreasing spine elimination.…”

Norepinephrine, olfactory bulb and memory stability

“…NpHR and Ctrl mice were trained under light stimulation in a 10-trial simultaneous go-no-go task (Escanilla et al, 2008, Chaudhury et al, 2009, Moreno et al, 2012, Mandairon et al, 2018 in which they had to associate odorant 1 with a reward while odorant 2 was not reinforced (Odorset 6; Supplementary Table 1). These 10 trials were immediately followed by 15 trials of reversal learning with no light stimulation in which odorant 1 was not reinforced and odorant 2 was rewarded ( Figure 1A).…”

“…Analysis was performed on the latency (delay) to dig in the rewarded dish as dependent variable. The latency to dig in the rewarded dish is a good indicator for the strength of the acquired memory, with short latencies signaling a strong memory and fast decision making and longer latencies signaling slower decision making and weaker learning (Mandairon et al, 2018). Repeated measures ANOVA were used to assess how blockade of NE projections modulates acquisition or recall.…”